The present invention relates to a new process for the stereospecific synthesis of D(+)-biotin.
Stereospecific syntheses of biotin starting from sugars of suitable configuration are known. Such a synthesis, starting from D-mannose, is described in Tetrahedron Letters No. 32, pages 2765-2766, 1975. An improved synthesis, starting from D-arabinose and continuing with the above-mentioned synthesis at the stage of the ester of 6,9-dihydroxy-7,8-isopropylidenedioxynonanoic acid is described in Liebig's Annalen der Chemie 1980, pages 1972-1977.
In the latter, the cyclic hemiacetal form of 3,4-isopropylidenearabinose is protected in the 2-position by a benzoyl group and reacted with a phosphorus ylide. Subsequent hydrogenation and cleavage of the protecting group leads to the above-mentioned ester of nonanoic acid, which can be converted to D(+)-biotin in a known manner.
However, even this improved synthesis is still not satisfactory, because a large number of reaction steps are necessary, which means that the overall yield is not very high.